Lyme disease is a multisystem infection caused by the tick-borne spirochete, B. burgdorferi (Steere, 1989). Because of the low yield of both culture and direct visualization techniques for identification of this organism, the diagnosis of Lyme disease has relied on serologic confirmation in patients with characteristic clinical findings.
Recognizing Lyme disease in the early stages can be difficult, however, because patients may not manifest the characteristic rash or may have only non-specific flu-like symptoms. This difficulty of diagnosis is compounded by the delayed emergence of a humoral response to the spirochete as detected by available serologic tests (Steere, 1989). These tests, which currently lack standardization, also do not readily distinguish between reactivity to B. burgdorferi proteins and cross-reactive proteins from commensual or other pathogenic organisms (Hansen et al., 1988; Magnarelli et al., 1987). Delay in establishing the diagnosis of Lyme disease in its early stages is clinically important because timely institution of appropriate antibiotic treatment can prevent the serious sequelae from this potentially chronic infection (Dattwyler et al., 1990; Steere et al., 1983).
Initial studies with immunoblot analysis of patients from North America with the early manifestations of Lyme disease found IgM reactivity predominantly against the 41 kDa flagellar protein of B. burgdorferi (Barbour et al., 1986; Craft et al., 1986). In hope of improving the level of detection of the antibody response in early Lyme disease, studies have utilized enriched preparations and recombinant forms of the 41 kDa flagellar protein as target antigen for serologic testing (Magnarelli et al., 1992; Coleman et al., 1987). This approach was prompted by the initial immunoblot studies with B. burgdorferi lysates in which an early and predominant IgM antibody response to the flagellar protein was demonstrated by Craft et al., 1986. Use of the flagellar protein-based serologic tests may be problematic because of the relatively frequent finding of cross-reactive antibodies to conserved flagellar epitopes from commonly occurring commensual and pathogenic spirochetes, such as those found in the mouth (Magnarelli et al., 1990; Russell et al., 1984).
Dressler et al. reported the most prominent IgM response in American patients with early disease was to a 21 kDa protein. This protein was reported to be reactive with a monoclonal antibody specific for pC. This finding contrasts with this same group's previous finding of a predominant early response to the 41 kDa flagellar antigen (Craft et al., 1986). The discrepency between these two findings was attributed to different antigen preparations despite the use of the same isolate, highlighting the potential confusion introduced by the current lack of test standardization.
Recently, Marconi et al. and Sadziene et al. localized the OspC gene to a 26-27 kDa circular plasmid, the first gene mapped to a circular plasmid in B. burgdorferi. Marconi et al. mapped the gene by using a variety of electrophoretic separation techniques and Southern blotting. Sadziene et al. used a group of B31-derived isolates which contained their linear chromosome and circular plasmids, but had been antibody-selected for the loss of a variable number of their linear plasmids. Sadziene et al. also found a correlation of an isolate's ability to express OspC and the loss of a linear plasmid of 16 kb (lp16). They hypothesized that a protein or RNA encoded by lp16 may function as a repressor of OspC expression. Loss of this plasmid could thereby lead to the loss of repression and new expression of the protein. In addition, these workers noted that the loss of lp16 also led to a failure of the mutant to grow on solid medium.